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Trial record 1 of 1 for:    ri-01-006 | Follicular Lymphoma
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Compare the Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in LTB Follicular Lymphoma (FLINTER) (FLINTER)

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ClinicalTrials.gov Identifier: NCT03976102
Recruitment Status : Recruiting
First Posted : June 5, 2019
Last Update Posted : April 9, 2020
Sponsor:
Collaborator:
Parexel
Information provided by (Responsible Party):
Dr. Reddy's Laboratories Limited

Study Description
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Brief Summary:

The primary objective of the current study is to demonstrate the equivalent efficacy of rituximab (DRL_RI) and MabThera® in subjects with Low Tumor Burden Follicular Lymphoma (LTB-FL).

Also evaluated by Pharmacokinetic, safety, and immunogenicity assessment between a proposed biosimilar (DRL_RI) and the RMP, as an component of clinical study program, and collectively providing the evidence of biosimilarity.

The study will compare the safety and efficacy of DRL_RI vs MabThera in patients with Low Tumor Burden Follicular Lymphoma (LTB-FL). The primary objective is to establish comparative efficacy as measured by ORR at week 28


Condition or disease Intervention/treatment Phase
Follicular Lymphoma Biological: DRL_RI (Proposed rituximab biosimilar) Other: MabThera® Phase 3

Detailed Description:

It is planned to randomise approx. 284 subjects at approximately 130 study sites worldwide. Subjects with LTB-FL will be randomized to receive either DRL_RI or MabThera®. Till date, 68 patients have been randomized for the study.

The study specific objectives are mentioned below:

Primary Objective:

  • To demonstrate the equivalent efficacy of DRL_RI (biosimilar rituximab) and MabThera in subjects with CD20-positive, LTB FL, as measured by overall response rate (ORR) at Week 28 Secondary Objectives:
  • To compare the progression-free survival (PFS), overall survival (OS), and duration of response (DOR) of DRL_RI with MabThera in subjects with CD20-positive, LTB FL.
  • To compare the safety, tolerability, and immunogenicity of DRL_RI with MabThera in subjects with CD20-positive, LTB-FL.

Exploratory Objectives

  • To explore the pharmacokinetic (PK) parameters of DRL_RI and MabThera, using a population-PK modelling approach.
  • To explore the pharmacodynamic parameters of DRL_RI and MabThera.
Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 284 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Clinical Phase III, randomised, multicentre, double-blind study to demonstrate the equivalence of DRL_RI to MabThera® in subjects with previously untreated, LTB-FL.
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: A Double-blind, Parallel-group, Phase III Study to Compare the Efficacy, Safety, and Immunogenicity of Proposed Rituximab Biosimilar (DRL_RI) With MabThera® in Subjects With Previously Untreated (CD)20-Positive LTB Follicular Lymphoma
Actual Study Start Date : February 1, 2019
Estimated Primary Completion Date : September 1, 2020
Estimated Study Completion Date : September 1, 2020

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Lymphoma
Drug Information available for: Rituximab

Arms and Interventions
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Arm Intervention/treatment
Experimental: Arm A: DRL_RI
DRL_RI (rituximab-Dr. Reddy's Lab) for infusion 375 mg/m2 administered via IV infusion on Days 1, 8, 15, 22 and Weeks 12, 20, 28 and 36
 Biological: DRL_RI (Proposed rituximab biosimilar)
Proposed rituximab biosimilar, 100mg and 500mg, concentrate for solution for infusion
Active Comparator: Arm B: MabThera®
MabThera® for infusion 375 mg/m2 administered via IV infusion on Days 1, 8, 15, 22 and Week 12, 20, 28 and 36.
 Other: MabThera®
Reference product rituximab, 100mg and 500mg, concentrate for solution for infusion


Outcome Measures
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Primary Outcome Measures :
  1. Overall Response Rate (ORR) measured for follicular lymphoma [ Time Frame: Month 7 (Week 28) ]
    The primary endpoint is ORR, defined as the proportion of subjects in each treatment group that achieve complete response (CR), unconfirmed complete response (CRu) or partial response (PR) at Month 7 (Week 28) with the response criteria for malignant lymphoma


Secondary Outcome Measures :
  1. Progression-free survival [ Time Frame: 52 Weeks ]
    Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL

  2. Overall response rate [ Time Frame: 12 Weeks ]
    Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL

  3. Overall survival [ Time Frame: 52 Weeks/End of Study ]
    Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL

  4. Duration of response [ Time Frame: 52 Weeks/End of Study ]
    Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL

  5. Safety in terms of Adverse Events [ Time Frame: 52 Weeks ]
    Compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL in terms of Adverse events (AEs) as assessed by the NCI CTCAE version 5.0.

  6. Tolerability in terms of Adverse Events [ Time Frame: 52 Weeks ]
    Compared between DRL_RI with MabThera® for subjects with severity (Grade 3 or Higher) of Treatment Emergent Adverse Events, as assessed by the NCI CTCAE v5.0.

  7. Analysis of BAb and NAb in Blood [ Time Frame: 52 Weeks ]
    Immunogenicity compared between DRL_RI with MabThera® in subjects with CD20 positive, LTB FL in terms of Anti-DRL_RI antibodies


Other Outcome Measures:
  1. Overall Response Rate (52 Weeks) [ Time Frame: 52 Weeks ]
    Overall response rate based on the Lugano criteria for those subjects with available positron emission tomography (PET) data, treated with either DRL_RI or MabThera®

  2. Volume distribution [ Time Frame: 52 weeks ]
    Pharmacokinetic parameter volume distribution for DRL_RI and MabThera® will be derived using a population-PK modeling approach.

  3. Clearance [ Time Frame: 52 weeks ]
    Pharmacokinetic parameter drug clearance for DRL_RI and MabThera® will be derived using a population-PK modeling approach.

  4. AUEC of B-cell depletion-time curve [ Time Frame: 52 Weeks ]
    Potential differences in pharmacodynamics parameter area under the effect curve (AUEC) of the B-cell depletion-time curve for DRL_RI and MabThera®


Eligibility Criteria
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Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  1. Subject is Male or female subjects aged ≥18 years of age.
  2. Subject is histologically confirmed, Grade 1-3a, previous ly untreated, CD20-pos itive.
  3. Subject has Ann Arbor Stage II to IV and ECOG status of 0 to 1.
  4. Subject has Low tumor burden follicular lymphoma as per Groupe d'Etude des Lymphomes Folliculaires (GELF) Criteria

  5. Subject has at least 1 measurable tumor mass in 2 dimensions, and the mass must be:

    1. Nodal lesion >15 mm in the longest dimension; or
    2. Noda l lesion >10 mm to he longest dimension; dimens ion and >10 mm in the shortest dimension; or
    3. Extra-nodal lesion with both long and short dimensions ≥10 mm.
  6. Subject has Life expectancy ≥3 months.
  7. If female subject, then subject should be non-pregnant, non-lactating.

Exclusion Criteria:

  1. Subject with prior use of rituximab or any CD20 monoclonal antibody for any reason.
  2. Subjects with known hypersensitivity to rituximab or its excipients, or to proteins of murine or other foreign origin.
  3. Any prior therapy for follicular lymphoma (including but not limited to chemotherapy, radiotherapy) or subjects on chronic supra-substitutive doses of systemic gluco-corticosteriods.
  4. Subjects who, in the opinion of the Investigator, require additional concomitant treatment for lymphoma.
  5. Evidence of histologic transformation to high grade lymphoma or diffuse large B-cell lymphoma.
  6. Subjects with known sero-positivity for or history of active viral infection with human immunodeficiency virus (HIV), hepatitis B surface antigen (HBsAg) positive or hepatitis B core antibody positive, hepatitis C virus (HCV) antibody positive.
  7. Subjects who have received a live vaccine within last 3 months of the first administration of study drug.
  8. Subjects with history or presence of a medical condition or disease that in the Investigator's opinion would place the subject at an unacceptable risk for study participation.
  9. Participation in any clinical study or having taken any investigational therapy (within 2-months of the first dose of study drug.
  10. Women of childbearing potential who do not consent to use highly effective methods of birth control.
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03976102


Contacts
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Contact: Narendra Maharaj, MBBS, MD +914044644500 narendramaharaj@drreddys.com
Contact: Sonica S Batra, MBBS, MD +914044644500 sonicabatra@drreddys.com

Locations
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United States, Maryland
Rcca Md Llc Recruiting
Bethesda, Maryland, United States, 20817
United States, Texas
University Cancer & Diagnostic Centers Recruiting
Houston, Texas, United States, 77089
Sponsors and Collaborators
Dr. Reddy's Laboratories Limited
Parexel
Investigators
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Study Director: Carina Flemmig, MD Parexel
More Information
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Responsible Party: Dr. Reddy's Laboratories Limited
ClinicalTrials.gov Identifier: NCT03976102    
Other Study ID Numbers: RI-01-006
First Posted: June 5, 2019    Key Record Dates
Last Update Posted: April 9, 2020
Last Verified: April 2020

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Studies a U.S. FDA-regulated Drug Product: Yes
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Dr. Reddy's Laboratories Limited:
Follicular Lymphoma
Dr. Reddy's Rituximab
Biosimiliar (DRL_RI)
FLINTER
Additional relevant MeSH terms:
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Lymphoma
Lymphoma, Follicular
Lymphoma, Non-Hodgkin
Neoplasms by Histologic Type
Neoplasms
Lymphoproliferative Disorders
Lymphatic Diseases
Immunoproliferative Disorders
 Immune System Diseases
Rituximab
Antineoplastic Agents, Immunological
Antineoplastic Agents
Immunologic Factors
Physiological Effects of Drugs
Antirheumatic Agents